Multiple myeloma patients receiving pre-emptive donor lymphocyte infusion after partial T-cell-depleted allogeneic stem cell transplantation show a long progression-free survival

Levenga, Henriëtte; Levison-Keating, S.; Schattenberg, A.V.M.B.; Dolstra, Harry; Schaap, Nicolaas; Raymakers, Reinier

doi:10.1038/sj.bmt.1705742

Cited by 17 publications

(6 citation statements)

References 20 publications

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“…Again, these data emphasize the role of DLI as being effective in low tumor burden state. 69% of these 13 patients were long term survivors [110]. …”

Section: Discussionmentioning

confidence: 99%

Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited

Deol

Lum

2010

Cancer Treatment Reviews

131

130

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“…Again, these data emphasize the role of DLI as being effective in low tumor burden state. 69% of these 13 patients were long term survivors [110]. …”

Section: Discussionmentioning

confidence: 99%

Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited

Deol

Lum

2010

Cancer Treatment Reviews

131

130

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“…In relapsed acute leukemia, a combination of gene transcript levels and four color flow cytometry, MRD monitoring has been found to predict a second relapse post-DLI (66). In myeloma, several groups have studied prophylactic or preemptive DLI (67–69), the rate of durable remissions is low, but secondary treatment is efficacious and survival is excellent.…”

Section: Prophylactic and Preemptive DLImentioning

confidence: 99%

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

et al. 2017

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The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

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“…116,117 The best results can be achieved at a stage of minimal residual disease, in patients in remission after chemotherapy. 118 Seven of 20 patients with complete remission (N ϭ 4) and partial remission (N ϭ 16) remained in continuous complete remission more than 4 years after partial T cell-depleted stem cell transplantation and preemptive donor lymphocyte transfusions (actuarial 6-year survival, 29%). The response of multiple myeloma to donor lymphocyte transfusion is not predictable and, in advanced disease relapses, often occurs outside the marrow cavity.…”

Section: Multiple Myelomamentioning

confidence: 99%

Graft-versus-leukemia effects of transplantation and donor lymphocytes

Kolb

2008

Blood

517

403

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Allogeneic transplantation of hematopoietic cells is an effective treatment of leukemia, even in advanced stages. Allogeneic lymphocytes produce a strong graftversus-leukemia (GVL) effect, but the beneficial effect is limited by graft-versushost disease (GVHD). Depletion of T cells abrogates GVHD and GVL effects. Delayed transfusion of donor lymphocytes into chimeras after T cell-depleted stem cell transplantation produces a GVL effect without necessarily producing GVHD. Chimerism and tolerance provide a platform for immunotherapy using donor lymphocytes. The allogeneic GVL effects vary from one disease to another, the stage of the disease, donor histocompatibility, the degree of chimerism, and additional treat- IntroductionTreatment of leukemia and other malignancies of the hematopoietic system with total body irradiation (TBI) and transplantation of bone marrow from healthy persons was developed from studies on radiation protection in the 1950s. However, it was evident from bioassays of murine leukemia that radiation could not eliminate leukemia in doses tolerated clinically. 1 In contrast, TBI followed by allogeneic marrow transplantation could cure leukemia in some murine models. 2 The term adoptive immunotherapy by allogeneic marrow transplantation was coined by Mathé 3 in the early 1960s when little was known about donor selection, appropriate conditioning treatment, and prevention of graft-versus-host disease (GVHD). Selection of sibling donors by human leukocyte antigen (HLA) typing, the combination of TBI with cyclophosphamide for conditioning treatment, and postgrafting immunosuppressive treatment with methotrexate provided the basis of success in the treatment of acute leukemia with allogeneic marrow transplantation. 4,5 In these patients, Weiden et al described the beneficial effect of GVHD on the incidence of leukemia relapse. 6 In patients with chronic GVHD, this reduced relapse was even associated with a survival benefit. 7 The role of T cells became evident when depletion of T cells from the graft was introduced into the clinical practice for prevention of GVHD. 8,9 In chronic myelogenous leukemia (CML), the beneficial effect of T-cell depletion on GVHD was negated because of an increased relapse rate. 10 Increased relapse after T-cell depletion was most pronounced in CML, less in acute myeloid leukemia (AML), and lowest in acute lymphoblastic leukemia (ALL). 11 The challenge of allogeneic stem cell transplantation for treatment of leukemia and other malignancies of the hematopoietic system is the prevention of GVHD without losing the graft-versusleukemia (GVL) effect. One possible approach has been is to apply a delayed transfusion of T cells after T cell-depleted marrow transplantation. Previous experiments in stable canine chimeras showed that graft-versus-host tolerance was not abrogated by donor lymphocyte transfusions (DLTs). 12 In DLA-identical littermate chimeras, we analyzed at which time after T cell-depleted marrow transplantation we could transfuse donor lymphocytes without p...

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Multiple myeloma patients receiving pre-emptive donor lymphocyte infusion after partial T-cell-depleted allogeneic stem cell transplantation show a long progression-free survival

Cited by 17 publications

References 20 publications

Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited

Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Graft-versus-leukemia effects of transplantation and donor lymphocytes

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